Study on the Long-Term Risk of Dementia in Parkinson’s Disease

Background

Parkinson’s Disease (PD) is a common neurodegenerative disorder primarily characterized by motor dysfunction. However, cognitive decline and Parkinson’s disease dementia (PDD) are also significant non-motor symptoms of PD. Although dementia occurs in approximately 80% of PD patients in colloquial terms, this data is mainly derived from studies conducted over twenty years ago, often with small sample sizes and other limitations. Therefore, the authors aim to reassess the long-term risk of dementia in PD patients through two large prospective observational studies.

Study Sources

This paper is authored by Julia Gallagher, Caroline Gochanour, Chelsea Caspell-Garcia, and several other scholars, mainly from institutions such as the University of Pennsylvania, University of Iowa, Rutgers University, King’s College London, and Columbia University. The study was published in the 2024 issue 103 of the journal Neurology, with paper number e209699.

Research Methods

Study Design

The research comprises two parts: one part is the international multi-center Parkinson’s Progression Markers Initiative (PPMI) project; the other part is the long-term PD research cohort at the University of Pennsylvania (Penn cohort).

PPMI Research Project:

• Sample Collection: Untreated new-onset PD patients and healthy controls (HC) were recruited from 24 research sites. Participants underwent annual cognitive assessments, and cognitive status was diagnosed by onsite researchers.
• Sample Characteristics: A total of 417 PD patients (average age 61.6 years, 65% male).
• Cognitive Assessment: Annual assessments using the Montreal Cognitive Assessment (MoCA) and the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Dementia proxies were defined as MoCA scores <21 and MDS-UPDRS Part 1 cognitive scores ≥3.

Penn Cohort:

• Sample Collection: Recruited from the tertiary movement disorder center at the University of Pennsylvania. Comprehensive cognitive assessments were conducted annually or biennially, with cognitive diagnoses made by expert consensus.
• Sample Characteristics: A total of 389 PD patients (average age 69.3 years, 67% male).
• Follow-Up: Annual or biennial follow-ups were conducted to record dementia incidence data.

Data Analysis

• Survival Curve Fitting: A non-parametric expectation-maximization iterative convex minorization algorithm was used to fit the time from PD diagnosis to a stable dementia diagnosis.
• Sensitivity Analysis: Worst-case sensitivity analysis was conducted for participants with missing data to estimate the incidence of dementia.

Experimental Results

Incidence of Dementia

• PPMI Cohort:

  • Estimated 10-year disease duration dementia probability: 9% (diagnosed by onsite researchers), 15% (MoCA scores), 12% (MDS-UPDRS Part 1 cognitive diagnosis).
  • During the overall follow-up period, 34 patients (8.5%) were diagnosed with dementia.

• Penn Cohort:

  • Estimated 10-year disease duration dementia probability: 27%.
  • Median time to dementia onset was 15 years (95% confidence interval 13–15 years).

Other Factors Affecting Dementia Risk

• Age: The older the age at PD diagnosis, the shorter the time to dementia onset. Median time to dementia onset was 19.4 years for the <56 age group, 14.6 years for the 56–70 age group, and 9.2 years for the >70 age group.
• Gender: Male patients had a higher risk of dementia than females. The median time to dementia onset for males was 13.3 years, while for females it was 19.4 years.
• Education Level: Patients with less than 13 years of education experienced faster dementia progression, with a median time to dementia onset of 11.6 years, compared to 15.2 years for those with 13 or more years of education.

Discussion

The study results indicate that the risk of dementia in PD patients may be lower than previously reported or may occur later in the disease progression. Further comparisons show that increasing age, being male, and lower education levels are predictive factors for the onset of dementia.

The significant differences between the two cohort studies may be attributed to various factors. For example, the PPMI cohort recruited patients early in the disease and untreated, whereas the Penn cohort consisted of patients from routine clinical care with more detailed cognitive assessments.

Conclusion and Clinical Significance

Combining data from the two cohorts, the risk of dementia as the disease progresses is as follows: 3-12% at 5 years, 9-27% at 10 years, 50% at 15 years, 74% at 20 years, and 90% at 25 years or later. These results provide more up-to-date and accurate long-term dementia risk estimates for PD patients, offering a longer window for further intervention and delay of cognitive decline.

Study Highlights

• Large Sample Size: Both cohorts are large-scale prospective studies in recent years.
• Rigorous Assessment: Detailed cognitive assessment tools and reliable diagnostic processes were used.

The findings of this study provide PD patients and healthcare practitioners with more accurate long-term dementia risk assessments, encouraging further research and therapeutic development in this field.